In a living body producing energy by aerobic respiration, a variety of an active oxygen is generated in the process. An active oxygen is a chemical species having higher reactivity than oxygen in the atmosphere. For example, a superoxide anion, a hydroxy radical, a singlet oxygen, hydrogen peroxide, a hydroperoxy radical and so on are known. It is known that excessive active oxygens generated in a cell non-specifically react with molecules in a living body such as a nucleic acid, a protein and a lipid to damage the cell and that they are involved with various diseases including metabolic syndrome such as diabetes, high blood pressure, hyperlipidemia and arteriosclerosis, a liver disease, a digestive system disease, a brain dysfunction disease, a cardiovascular system disease, cardiac hypofunction, a cancer, atopic dermatitis and so on. For this reason, it is indispensable to remove excessive active oxygens for maintaining the life of an aerobic organism, and there is an oxidation defense mechanism using antioxidant enzymes or antioxidant substances. The antioxidant enzymes are enzymes that remove specific active oxygens. For example, superoxide dismutase (SOD), peroxidase, catalase and so on are known. Antioxidant substances are substances that detoxify active oxygens by its own oxidization (elimination of singlet oxygen is partly caused by energy transfer) and, for example, carotenoids such as astaxanthin, zeaxanthin, canthaxanthin, lutein and β-carotene, vitamins such as vitamin C and vitamin E, α-lipoic acid, and glutathione are known.
Among carotenoids, it is known that astaxanthin, which has particularly excellent anti-oxidation activity, is useful in, for example, fields of a photolesion disease, an ophthalmic disease, a dermatologic disease, an inflammation disease, an immune disease, a cardiac disease, a malignant tumor disease, a liver disease, a kidney disease, a neurodegenerative disease, an addictive disease, an allergic disease, an insulin-resistant disease, a diabetic disease, a hyperlipidemia disease, a cardiac function disease, a vascular system disease and so on (Non Patent Literatures 1 and 2). It is useful as a therapeutic agent, a preventive agent and so on in various diseases in which an active oxygen participates, for example, ocular diseases such as retinopathy (including diabetic retinopathy), (age-related) macular degeneration, cataract and dry eye, metabolic syndromes such as diabetes, high blood pressure, hyperlipidemia and arteriosclerosis, liver diseases such as alcoholic liver disease, non-alcoholic steatohepatitis (NASH), a viral or drug-induced liver disease and steatohepatitis, kidney diseases such as glomerulonephritis, kidney failure and diabetic nephropathy, digestive system diseases such as reflux esophagitis, stomach ulcer, duodenal ulcer and an inflammatory bowel disease, brain dysfunction diseases such as a cerebrovascular disorder and dementia, cardiovascular system diseases such as myocardial infarction, angina pectoris, heart failure, arrhythmia and myocarditis, cardiac hypofunction, cancer, skin diseases such as atopic dermatitis, wound and bedsore, neurodegenerative diseases such as amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's syndrome and diabetic neuropathy, sarcopenia and so on.
Meanwhile, it is known that digestive absorption of astaxanthin is very low, and the biological availability is around several percent. For example, when astaxanthin originated from Haematococcus algae (containing esters of fatty acids as a main component) is administered in 9 mg/day (as a conversion to a free form of astaxanthin) to a human, Cmax in the blood plasma is 77.15 ng/mL, and AUC (0-72 h) is 1683 ng·h/mL (Non Patent Literature 3). One factor conceivable for this is that carotenoids such as astaxanthin has extremely high hydrophobicity and lacks water solubility. This is also a cause for a limited administration form of astaxanthin to a warm-blooded animal (particularly, human). For that reason, astaxanthin derivatives having further water solubility are considered to be useful and a preparation method therefor has been reported (Patent Literatures 1 and 2).